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Both epidemiologic and cellular studies in the context of autoimmune diseases have established that protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is a key regulator of T cell receptor (TCR) signaling. However, its mechanism of action in tumors and its translatability as a target for cancer immunotherapy have not been established. Here, we show that a germline variant of PTPN22, rs2476601, portended a lower likelihood of cancer in patients. PTPN22 expression was also associated with markers of immune regulation in multiple cancer types. In mice, lack of PTPN22 augmented antitumor activity with greater infiltration and activation of macrophages, natural killer (NK) cells, and T cells. Notably, we generated a small molecule inhibitor of PTPN22, named L-1, that phenocopied the antitumor effects seen in genotypic PTPN22 knockout. PTPN22 inhibition promoted activation of CD8(+) T cells and macrophage subpopulations toward MHC-II–expressing M1-like phenotypes, both of which were necessary for successful antitumor efficacy. Increased PD-1/PD-L1 axis expression in the setting of PTPN22 inhibition could be further leveraged with PD-1 inhibition to augment antitumor effects. Similarly, cancer patients with the rs2476601 variant responded significantly better to checkpoint inhibitor immunotherapy. Our findings suggest that PTPN22 is a druggable systemic target for cancer immunotherapy.

As a newly emerging approach for surface-enhanced Raman spectroscopy (SERS), pressure-induced SERS (PI-SERS) has been attracting increasing interest for its applications in Raman signal enhancement at extreme conditions. However, how to efficiently realize the PI-SERS enhancement and elucidate the corresponding mechanism remain open questions. Herein, we demonstrate the PI-SERS enhancement up to 8.04 GPa using monolayer molybdenum disulfide (ML-MoS

Here, we report a high-pressure study on corannulene up to 27.6 GPa using the diamond cell technique assisted by Raman and infrared spectroscopic measurements. The intermolecular interactions betwe...

We report the high stability and reversibility of disordered graphitic nanocarbon (DGN) under high pressure. No bonding change can be observed in DGN even up to 52.0 GPa and it fully recovers upon decompression. The high stability and reversibility should be related to its unique highly disordered structure which consists of nanosized wavy graphene layers, making the DGN elastic upon compression. Combined with high temperature, DGN is transformed into polycrystalline nanodiamonds with average grain size smaller than the pristine nanoparticles.

Aerogel films have been widely used in various fields due to their fantastic properties. Diamond aerogel film is expected to possess the advantages of both film materials and aerogel like materials, but still has not been realized up to now. Here, we provide a feasible way to prepare freestanding, transparent aerogel-like diamond nanofilm (ADF) by treating glassy carbon nanofilm (GCF) at high pressure and high temperature (HPHT). The ADF is constructed by interconnected ultra-small diamond nanograins and possess a porous aerogel-like microstructure, while inherits a film morphology of the parent glassy carbon. The growth of ADF has been discussed in the framework of a melting and diffusion process, in which the low density and low thickness of GCF precursor favor the aerogel formation under HPHT. Further insight into the formation of such unique ADFs has been presented. The aerogel-like diamond nanofilm adds a new member into diamond film family and may expand the applications of this type of porous nanofilm.

When the harvester travels in the field, road excitation will cause low-frequency vibration within 3 Hz, which is the most sensitive frequency range of human body. In order to evaluate the influence of road excitation on the comfort feelings of the harvester driver, vibration acceleration data were collected when the combine harvester was travelling at high and low speeds on flat-soft road, flat-solid road, and rough-solid road. The vibration comfort of the harvester was evaluated by root mean square (RMS) of weighted acceleration. The results showed that the speed of harvester, road surface roughness and hardness have great effects on harvester vibration comfort. Soft road has an obvious absorption effect on the vibration at 70 Hz. The increase in the speed of harvester and road surface hardness and roughness elevates the subjective discomfort of the driver. Keywords: Combine harvester, Comfort research, Road excitation, Root mean square of weighted acceleration, Vibration test.

Pressure-induced surface-enhanced Raman spectroscopy (PI-SERS) represents a new frontier in the research field of SERS. However, relatively few studies have focused on PI-SERS due to many difficulties, such as easy aggregation of nanoparticles, and difficulty in understanding the interaction mechanisms between probe molecules and the SERS substrate at high pressure. Here we developed an efficient semiconductor-metal SERS substrate (MoS2/Au) to study PI-SERS. Different from the previously reported monotonous decrease in Raman intensities upon compression, an anomalous Raman enhancement of R6G molecules adsorbed on the MoS2/Au substrate was observed up to 2.39 GPa, at which the degree of charge transfer (ρCT) between the R6G molecules and the MoS2/Au substrate reaches a maximum. By comparison, it is proposed that the decoration of Au on the SERS system could bring about a two-step charge transfer (CT) process, introduce localized surface plasmon resonance (LSPR), and thus favor the PI-SERS enhancement. Moreover, this charge transfer also causes obvious changes in the optical behaviors of R6G molecules upon compression. This brings new insights into the SERS study and also offers new ideas for the development of SERS application in high pressure studies.

A large body of research has established diabetes-related cognitive deterioration, sometimes known as "diabetic encephalopathy". Current evidence supports that oxidative stress, neuronal apoptosis, and cerebral microcirculation weakness are associated with cognition deficits induced by diabetes. The present study explores the effect of propionate on neurological deficits, cerebral blood flow, and oxidative stress in diabetic mice. Propionate in different doses (37.5, 75 and 150 mg/kg) was orally administrated daily. Here, we show that propionate can markedly improve neurological function, which is correlated with its capabilities of stimulating nitrogen monoxide (NO) production, increasing cerebral microcirculation, suppressing oxidative stress, and reducing neuron loss in the hippocampus. In addition, the results of Western Blotting indicated that the brain-protective function of propionate in streptozocin (STZ)-induced type 1 diabetes mellitus (T1DM) mice is related to phosphoinositide 3-kinase (PI3K)/serine-threonine protein kinase (Akt)/endothelial nitrogen monoxide synthase (eNOS) signaling pathway. In a diabetic mouse model, propionate reduces cerebral microcirculation, hippocampus apoptosis, and neurological impairment. Thus, propionate, now employed as a food preservative, may also help slow diabetes-induced cognitive loss.

MYCN amplification is tightly associated with the poor prognosis of pediatric neuroblastoma (NB). The regulation of NB cell death by MYCN represents an important aspect, as it directly contributes to tumor progression and therapeutic resistance. However, the relationship between MYCN and cell death remains elusive. Ferroptosis is a newly identified cell death mode featured by lipid peroxide accumulation that can be attenuated by GPX4, yet whether and how MYCN regulates ferroptosis are not fully understood. Here, we report that MYCN-amplified NB cells are sensitive to GPX4-targeting ferroptosis inducers. Mechanically, MYCN expression reprograms the cellular iron metabolism by upregulating the expression of TFRC, which encodes transferrin receptor 1 as a key iron transporter on the cell membrane. Further, the increased iron uptake promotes the accumulation of labile iron pool, leading to enhanced lipid peroxide production. Consistently, TFRC overexpression in NB cells also induces selective sensitivity to GPX4 inhibition and ferroptosis. Moreover, we found that MYCN fails to alter the general lipid metabolism and the amount of cystine imported by System Xc(−) for glutathione synthesis, both of which contribute to ferroptosis in alternative contexts. In conclusion, NB cells harboring MYCN amplification are prone to undergo ferroptosis conferred by TFRC upregulation, suggesting that GPX4-targeting ferroptosis inducers or TFRC agonists can be potential strategies in treating MYCN-amplified NB.

Based on CT scan, the finite element models of human arm were constructed. Modal analysis of the arm was performed, and the natural vibration characteristics were evaluated. The dynamic simulation of the vibration transmission process was carried out when grasping the handle, and the vibration response and transmission characteristics were investigated. Resonance was likely to occur in the ranges of 5-10 Hz and 35-40 Hz, which caused fatigue damage to the arm. Vibrations in the ranges should be avoided having direct contact with the handle. The analysis results were found to be consistent with those of modal analysis.

According to the laws of thermodynamics, materials normally exhibit contraction or expansion along the directions of the applied pressure or tension. Here, we show that a man-made cocrystal of a metallofullerene and highly energetic cubane, with strained sp

The fabrication of silicon (Si) anode materials derived from high silica-containing plants enables effective utilization of subsidiary agricultural products. However, the electrochemical performances of synthesized Si materials still require improvement and thus need further structural design and morphology modifications, which inevitably increase preparation time and economic cost. Here, the conversion of corn leaves into Si anode materials is reported via a simple aluminothermic reduction reaction without other modifications. The obtained Si material inherits the structural characteristics of the natural corn leaf template and has many inherent advantages, such as high porosity, amorphous/crystalline mixture structure, and high-valence SiO

Pressure-induced surface-enhanced Raman spectroscopy (PI-SERS) represents a new frontier in the research field of SERS. However, relatively few studies have focused on PI-SERS due to many difficulties, such as easy aggregation of nanoparticles, and difficulty in understanding the interaction mechanisms between probe molecules and the SERS substrate at high pressure. Here we developed an efficient semiconductor-metal SERS substrate (MoS

Graphite is known to transform into diamond under dynamic compression or under combined high pressure and high temperature, either by a concerted mechanism or by a nucleation mechanism. However, these mechanisms fail to explain the recently reported discovery of diamond formation during ambient temperature compression combined with shear stress. Here we report a new transition pathway for graphite to diamond under compression combined with shear, based on results from both theoretical simulations and advanced experiments. In contrast to the known model for thermally activated diamond formation under pressure, the shear-induced diamond formation takes place during the decompression process via structural transitions. At a high pressure with large shear, graphite transforms into ultrastrong $s{p}^{3}$ phases whose structures depend on the degree of shear stress. These metastable $s{p}^{3}$ phases transform into either diamond or graphite upon decompression. Our results explain several recent experimental observations of low-temperature diamond formation. They also emphasize the importance of shear stress for diamond formation, providing new insight into the graphite-diamond transformation mechanism.

Diamond aerogel, a special kind of carbon aerogel made by sp3 carbon atoms, has been attracting intensive research interest due to its potential applications since it is first synthesized by the conversion of amorphous carbon. Despite of many expectations in diamond aerogel, the study on its synthesis is still not adequate compared with other carbon aerogel. Here we report the synthesis of diamond aerogel by laser heating graphene aerogel (GA) under high pressure in a diamond anvil cell. The results suggest that the density and microstructure of GA, as well as the heating duration obviously affect the diamond aerogel growth. When heating GA with lower laser power, we also observe a transparent carbon phase in experiment, which transforms into graphite and amorphous carbon upon decompression. These results present new insights into our understanding on the transformation from ultralow density carbon to sp3 carbon under high pressure and high temperature. It is possible to tune the microstructures of diamon...

Carbon nitride (C-N) materials have been attracting great interest because of their extraordinary performance in photocatalysis and energy conversion. However, developing an effective strategy for achieving band-gap engineering of C-N materials to satisfy practical applications remains highly desired. Here we report an efficient way to tune the band gap and control the nitrogen stoichiometry in carbon nitride compounds by using high pressure and high temperature (HPHT) treatment. It is found that treating a g-C3N4 precursor at relatively low temperature (630oC and below) under pressure can efficiently narrow the band gap even down to the red light region (~600 nm), increase the crystallinity, and significantly improve the charge carrier separation efficiency (by two orders of magnitude), almost without changing their stoichiometry. When increasing the treatment temperature under pressure, nitrogen-doped graphene/graphite materials with weak ferromagnetism were obtained. We thus obtained C-N materials with tunable band gaps, ranging from semiconducting to metallic states. XPS measurements show that pyridinic nitrogen is preferentially eliminated under such HPHT conditions while graphitic nitrogen is preserved in the C-N network. Our results thus provide an efficient strategy for tuning the structure and physical properties of C-N materials for applications. Supplementary information available at the journal website.

The efficacy of traditional chemotherapy often suffers from rapid clearance and off-target toxicity. Drug delivery systems and controlled release are applied to improve the therapeutic efficiencies of small-molecule drugs. In this work, two novel oxidative/reductive (Ox/Re) -sensitive and one non-sensitive Paclitaxel (PTX) prodrugs were synthesized with a maleimide group, which rapidly conjugates with albumin in vivo. Albumin serves as a good vehicle to deliver more prodrug to tumors due to the enhanced permeation and retention (EPR) effect. PTX was then released from the prodrugs in glutathione(GSH)/ reactive oxygen species(ROS)-rich tumor microenvironments. This bioresponsive prodrug strategy demonstrates potent chemotherapeutic efficiency in vivo and may be utilized in clinical cancer therapy.

Li3V2(PO4)3 (LVP) has been highlighted as a promising cathode material for lithium ion batteries, but it suffers from poor rate capability and rapid capacity decay due to sluggish electrode kinetics and vigorous electrode/electrolyte side reactions at high voltage. In this study, an inexpensive aqueous lithium poly-acrylic acid (LiPAA) binder was developed to deftly solve the shortcomings of the LVP material by tailoring the functional groups in the binder. The good adhesion and cohesion properties of the LiPAA binder ensured a close linkage between the active LVP particles, conductive additives and current collector, which formed a stable and conductive network in the electrode. In addition, the reversible H+/Li+ exchange in LiPAA effectively assisted the transport of Li+ ions at the electrode interface, which allowed the establishment of a Li+ conductive pathway without considerable degradation of the electrolyte. Due to these advantages, the LVP electrode containing the LiPAA binder exhibited significantly improved electrochemical performance compared to the electrode that employed the traditional polyvinylidene fluoride binder. The new electrode configuration showed a large specific capacity of 107 mA h g−1 at 70C rate and a high capacity retention of 91% was obtained after 1400 cycles at 10C rate, showcasing the great potential of this aqueous binder in lithium ion batteries.

Nanostructured carbon is a low-cost, economic, and elementally abundant candidate for manufacturing high-conductivity counter electrodes of organic photoelectric devices. Herein, we prepare onion-like carbon nanosphere:silver (OLCNS:Ag) composite electrodes for efficient, inverted-architecture polymer solar cells (PSCs) via a simple, solution-processed approach. The optical electric field distribution from the OLCNS:Ag nanocomposite layer opens up the possibility of additional light harvesting of the entire visible spectrum resulting from synergies between both components. The large effective specific surface area and high conductivity of OLCNS allow significant charge transfer and collection, resulting in a remarkably enhanced power conversion efficiency (PCE) of 9.81% in PTB7:PC71BM PSCs and 6.95% in PCDTBT:PC71BM PSCs, compared with control devices with PCEs of 7.76 and 5.31%, respectively. These consequences indicate that OLCNS:Ag composite electrodes constitute a valid and versatile method for realiz...

Highlights The TTC layer was efficiently deposited at the grain boundary of the perovskite, which passivated the grain surface and grain boundary, thereby decreasing the interfacial recombination of the perovskite solar cells.The hydrophobic small molecule TTC on the perovskite films forms a water-resistant layer that protects the perovskite from water damage. Electronic supplementary material The online version of this article (10.1007/s40820-019-0282-0) contains supplementary material, which is available to authorized users., The advancement of perovskite solar cells (PVSCs) technology toward commercialized promotion needs high efficiency and optimum stability. By introducing a small molecular material such as tetratetracontane (TTC, CH3(CH2)42CH3) at the fullerene (C60)/perovskite interface of planar p-i-n PVSCs, we significantly reduced the interfacial traps, thereby suppressing electron recombination and facilitating electron extraction. Consequently, an improved efficiency of 20.05% was achieved with a high fill factor of 79.4%, which is one of the best performances for small molecular-modified PVSCs. Moreover, the hydrophobic TTC successfully protects the perovskite film from water damage. As a result, we realized a better long-term stability that maintains 87% of the initial efficiency after continuous exposure for 200 h in air. Electronic supplementary material The online version of this article (10.1007/s40820-019-0282-0) contains supplementary material, which is available to authorized users.

To overcome the intrinsic chemical-reduction-activity of highly p-doped PEDOT:PSS and improve the open-circuit voltage (Voc) of planar inverted perovskite solar cells, a kind of oxidized carbon nanorods (OCNRs) is developed by a ball-milling/chemical-oxidation method and incorporated into PEDOT:PSS hole transport layer (HTL). The incorporation of OCNRs can increase the work function of the PEDOT:PSS layer, which avoids the energy-level mismatch between the PEDOT:PSS HTL and the HOMO level of the CH3NH3PbI3 perovskite layer, leading to a relatively high Voc of 1.01 V (vs. 0.92 V for the PEDOT:PSS device). Moreover, the introduction of OCNRs into the PEDOT:PSS HTL increases the grain size and uniformity of the perovskite layer, accompanied by the improved charge transport ability. As a result, the fill factor of perovskite solar cells is increased from 75.4% to 81.7%, and the best power conversion efficiency of 19.02% is achieved.

The fabrication of silicon (Si) anode materials derived from high silica-containing plants enables effective utilization of subsidiary agricultural products. However, the electrochemical performances of synthesized Si materials still require improvement and thus need further structural design and morphology modifications, which inevitably increase preparation time and economic cost. Here, the conversion of corn leaves into Si anode materials is reported via a simple aluminothermic reduction reaction without other modifications. The obtained Si material inherits the structural characteristics of the natural corn leaf template and has many inherent advantages, such as high porosity, amorphous/crystalline mixture structure, and high-valence SiOx residuals, which significantly enhance the material's structural stability and electrode adhesive strength, resulting in superior electrochemical performances. Rate capability tests show that the material delivers a high capacity of 1200 mA h g-1 at 8 A g-1 current density. After 300 cycles at 0.5 A g-1 , the material maintains a high specific capacity of 2100 mA h g-1 , with nearly 100% capacity retention during long-term cycling. This study provides an economical route for the industrial production of Si anode materials for Lithium-Ion batteries.

In order to build the fusion models, the high performance liquid chromatographic (HPLC) fingerprints of scutellariae radix (SR), rhei radix et rhizoma (RRR), coptidis rhizoma (CR) and their synthesizing fingerprints were developed in this study. After exploring the consistency between the fingerprints of compound synthesizing fingerprints (CSF) and the sample, the quality of traditional Chinese medicine preparation was predicted intelligently using CSF. HPLC coupled with diode array detector was used to obtain chromatograms of SR, RRR, CR and Yi Qing Tablet (YQT) samples at 268 nm. Meanwhile, the quality of CSF and the 15 batches of YQT samples was evaluated by systematically quantified fingerprint method (SQFM) qualitatively and quantitatively. The chromatograms showed that CSF covered the main fingerprints' information of each herb and the 55 common peaks of CSF covered the main information of the 50 common peaks in YQT sample. The evaluation results showed that among the 15 batches of YQT samples, only YQT-S01 was grade 5 and the others were all above grade 3. Most of the CSFs were grade 2 or grade 1 except CSF-2 which was grade 6. The fingerprints of Chinese herba preparation could be replaced by CSF to achieve a novel pattern for predicting the quality of TCM preparation intelligently by studying the relationship between the standard fingerprints and the CSF, and simultaneously developing first-class evaluation software.

Onion-like carbon nanospheres (OCNSs) with an average diameter of 43 nm were produced on a large scale via a combustion method and examined as an anode material for lithium ion batteries. The OCNSs exhibit a remarkable electrochemical cycling behavior and a capacity much higher than that of graphite. The capacity increases significantly with increasing charge-discharge cycles and reaches a value of 178% of the initial value (from 586 mA h g-1to 1045 mA h g-1) after 200 cycles. Further investigation provides unambiguous experimental evidence that such a remarkable capacity increase is related to the stable onion-like structure of the OCNSs and to the existence of large numbers of disordered/short graphitic fragments, which gradually provide more active sites for Li ion storage. The unique electrochemical performance of OCNSs provides a new way to design a high-performance anode material for rechargeable batteries.

High pressure Raman spectra of graphdiyne (GDY) have been studied up to 34.63 GPa. We found that sp-hybridized carbons in GDY are highly active and start to undergo a bonding change at around 5.2 GPa. Such a bonding change affects the C-C stretching vibration of sp2 hexagon rings in GDY, leading to an anomaly in the corresponding G-band pressure coefficient. A three-dimensional sp2 structure is proposed to form via pressure-induced interlayer cross-linking of sp carbons in GDY and is stable up to at least 34.63 GPa. Our study presents an important example in the study of graphyne family under pressure.

As a new category of solids, crystalline materials constructed with amorphous building blocks expand the structure categorization of solids, for which designing such new structures and understanding the corresponding formation mechanisms are fundamentally important. Unlike previous reports, new amorphous carbon clusters constructed ordered carbon phases are found here by compressing C8H8/C60 cocrystals, in which the highly energetic cubane (C8H8) exhibits unusual roles as to the structure formation and transformations under pressure. The significant role of C8H8 is to stabilize the boundary interactions of the highly compressed or collapsed C60 clusters which preserves their long‐range ordered arrangement up to 45 GPa. With increasing time at high pressure, the gradual random bonding between C8H8 and carbon clusters, due to “energy release” of highly compressed cubane, leads to the loss of the ability of C8H8 to stabilize the carbon cluster arrangement. Thus a transition from short‐range disorder to long‐range disorder (amorphization) occurs in the formed material. The spontaneous bonding reconstruction most likely results in a 3D network in the material, which can create ring cracks on diamond anvils.

Carbon nano-onions (CNOs) with an average diameter of 43 nm have been studied under pressure. The interlayer d-spacings of the CNOs are expanded by about 3% compared to those of the larger CNOs with average diameter of 150 nm studied earlier. High pressure study on the G-band of the small CNOs indicates that a bonding change was initiated at 23.4 GPa, which is higher than that of the larger CNOs. The small CNOs were destroyed into amorphous fragments at above 48 GPa with a large applied deviatoric stress, showing a lower high pressure stability compared with the larger CNOs. These features are qualitatively similar to the size effects observed in the compression behavior of some nanocrystalline materials, showing that a reduced cluster size gives similar physical effects in the two classes of materials. The present results for CNOs can be rationalized by the interlayer expansion and the highly turbostratic layer structure of the studied material. The fact that CNOs with different diameters behave differently upon compression is important when selecting materials for applications.